Ectromelia, an orthopoxvirus, causes mousepox in colonized mice. Studies were carried out: 1) to improve the surveillance and control measures necessary to prevent future mousepox epizootics in the mouse colonies; and 2) to study the molecular basis of orthopoxvirus pathogenesis in inbred mice, and to apply the acquired knowledge towards the development of a safe, effective recombinant vaccinia virus vaccine for human use. 1) Mousepox control measures: These studies showed that the current practice of immunizing mice against mousepox with vaccinia virus IHD-T is of dubious value and should only be carried out in exceptional circumstances. It was also demonstrated that all cell lines (especially hybridomas) passed in mice potentially can become infected with ectromelia virus, and can result in new cases of mousepox on reinoculation into previously unexposed mice. 2) Virus pathogenesis studies: This research was expanded this year and carried out in two mutually supportive directions, firstly a number of different regions of the orthopoxvirus genome were evaluated for their contribution to virus virulence in mice and rabbits. The thymidine kinase and vaccinia growth factor genes were shown to contribute to virus virulence in the host, as well as a 9 kb protein coding region proximal to the left hand terminus of the genome. The second area of investigation involved the genetic analysis of inbred mouse strains in order to determine the number and importance of non-H-2 genes responsible for recovery from mousepox. The resistance genes segregated as a multifactorial dominant locus, and a portion of the resistance phenotype appeared to be sex-linked. Subsequent work will focus on the mechanism by which these genes protect the host from mousepox.